Cholinergic and adrenergic neurotransmission in brain is mediated in part through muscarinic and alpha-1-adrenergic receptor stimulated phosphoinositide hydrolysis. A variety of evidence suggests that cholinergic and adrenergic neurotransmission is disrupted during aging. The loss of cognitive function which occurs during normal aging, senile dementia and Alzheimer's disease is likely to be related to change in cholinergic neurotransmission during aging. The administration of muscarinic cholinergic antagonists produces memory deficits in young animals similar to those found to occur naturally in aged animals. An understanding of muscarinic cholinergic and alpha 1- adrenergic receptor stimulated phosphoinositide hydrolysis is essential for a complete understanding of the mechanisms of cholinergic and adrenergic transmission in brain. The long-term objective of this proposal is to determine the properties and mechanisms of adrenergic and cholinergic receptor coupling to phosphoinositide hydrolysis in brain and how these processes are altered during senescence.